Synapse formation, synapse termination, synapse specificity and neurotransmission were studied using neurons and muscle cells in culture. Synapses were detected and investigated by electrophysiological recording. Neurons from chick and rat retina form transient synapses with muscle cells, whereas neurons from chick spinal cord form long-lived synapses with muscle cells. Each type of neuron possesses a synapse-competent state in its development during which it can abundantly form synapses with muscle cells in culture. These results suggest a mechanism of synapse specificity based on stabilization of correct synapses coupled with a synaptogenic period during development for each type of neuron. In addition, it appears likely that a methyltransferase reaction is involved in neurotransmission.